In this study, 227 and 211 patients with CAD-QS and CAD-QD were enrolled, and all patients were treated with PCI. LFQ quantitative proteomics technology was used to analyze the changes of serum protein fingerprints of patients before and 6 months after PCI, to explore the intervention mechanism of PCI on CAD of two different TCM syndromes. Clinical results showed that TNF- α, HDL-C, BSCSO, and Gensini levels were significantly changed in both groups after PCI; Proteomic results showed that there were 79 and 95 DEPs in CAD (QS) and (QD) respectively. Changes in the levels of C8A, CFH, APOH, APOB, PLG, and CFI were found in both groups after PCI, mainly involving biological processes such as complement and coagulation cascade, lipid metabolism, vascular function regulation, immunity and inflammation. In addition, cell adhesion and connection-related processes were found in QS patients after PCI, QD group showed the changes of lipid metabolism-related pathways such as the PPAR signal pathway and ECM receptor interaction after PCI. In conclusion, this study provides information on the changes of serum proteome after CAD QS and QD PCI and provides a reference for further research on CAD proteome and identification of biomarkers related to PCI intervention in CAD subtypes.